Mice are protected from Helicobacter pylori infection by nasal immunization with attenuated Salmonella typhimurium phoPc expressing urease A and B subunits.
Live Salmonella typhimurium phoPc bacteria were tested as mucosal vaccine vectors to deliver Helicobacter pylori antigens. The genes encoding the A and B subunits of H. pylori urease were introduced into S. typhimurium phoPc and expressed under the control of a constitutive tac promoter (tac-ureAB) or a two-phase T7 expression system (cT7-ureAB). Both recombinant Salmonella strains expressed the two urease subunits in vitro and were used to nasally immunize BALB/c mice. The plasmid carrying cT7-ureAB was stably inherited by bacteria growing or persisting in the spleen, lungs, mesenteric or cervical lymph nodes, and Peyer's patches of immunized mice, while the plasmid carrying tac-ureAB was rapidly lost. Spleen and Peyer's patch CD4+ lymphocytes from mice immunized with S. typhimurium phopc cT7-ureAB proliferated in vitro in response to urease, whereas cells from mice given S. typhimurium phoPc alone did not. Splenic CD4+ cells from mice immunized with phoPc cT7-ureAB secreted gamma interferon and interleukin 10, while Peyer's patch CD4+ cells did not secrete either cytokine. Specific H. pylori anti-urease immunoglobulin G1 (IgG1) and IgG2A antibodies were detected following immunization, confirming that both Th1- and Th2-type immune responses were generated by the live vaccine. Sixty percent of the mice (9 of 15) immunized with S. typhimurium phoPc cT7-ureAB were found to be resistant to infection by H. pylori, while all mice immunized with phoPc tac-ureAB (15 of 15) or phoPc (15 of 15) were infected. Our data demonstrate that H. pylori urease delivered nasally by using a vaccine strain of S. typhimurium can trigger Th1- and Th2-type responses and induce protective immunity against Helicobacter infection.
Corthésy-Theulaz
I E
IE
Department of Internal Medicine CHUV, and Institute of Pathology, Lausanne University, Switzerland. Irene.CorthesyTheulaz@ipharm.unil.ch
Hopkins
S
S
Bachmann
D
D
Saldinger
P F
PF
Porta
N
N
Haas
R
R
Zheng-Xin
Y
Y
Meyer
T
T
Bouzourène
H
H
Blum
A L
AL
Kraehenbuhl
J P
JP
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D016481:Helicobacter Infections / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000201:enzymology; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D012486:Salmonella typhimurium / Q000235:genetics*; D014169:Transformation, Bacterial; D014510:Urease / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D014614:Vaccines, Synthetic; D014510:Urease